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Genes May Determine Lung Cancer Risk

CancerWise -
June 2008

A common, inherited genetic variation may help explain why some smokers are more likely to develop lung cancer than others.

Significance of results

While all smokers and former smokers are at increased risk for lung cancer, fewer than 20% develop the disease. The genetic variations identified in the study, which were present in about half the population studied, suggest new mechanisms influencing lung cancer development.

"This is the first study to identify a common genetic variant that influences the risk for developing lung cancer," says the study’s lead author Chris Amos, Ph.D., professor in M. D. Anderson's Department of Epidemiology.

Amos and other M. D. Anderson scientists who led the multi-center research team reported the results in the April 2 online edition of Nature Genetics. Researchers from Johns Hopkins University, the Institute for Cancer Research and the University of Cambridge also participated in the study.

Primary results

The genetic variations involve two single-nucleotide polymorphisms (SNPs) on chromosome 15. SNPs are places in the human genome that vary by a single DNA chemical building block or nucleotide. Alleles (different forms of the same gene) at the two SNPs that were studied tend to co-occur in Caucasian individuals, so that scientists think they point to only a single genetic variant influencing lung cancer risk.

People who have smoked and who have one or two copies of these SNPs have a 28% to 81% greater chance of developing lung cancer, Amos says.

The study also found that three of the five genes in the area of chromosome 15 serve as receptors, or docking sites, to which nicotine can bind. This finding supports a growing body of evidence that nicotine, long known as the prime addictive compound in cigarettes, might cause lung cancer.

Additional results

Researchers in another study reported by Hung and colleagues in Nature did not find any association of these SNPs with either head and neck cancers or espophageal cancer. Amos and colleagues reported no association of these SNPs with lung cancer in those who have never smoked, suggesting that a combination of both genetic factors and tobacco smoking is needed to unmask the harmful effects of the variant in this region.

Research methods

Researchers obtained genetic samples from former and current smokers in Houston who participated in a long-term, 17-year M. D. Anderson study of the epidemiology of lung cancer. Participants were tested for about 314,000 SNP markers.

The participants included:

1,154 who had developed lung cancer

1,137 who had not developed lung cancer

Another group of scientists conducted the same genetic studies in the United Kingdom.

Those participants included:

2,013 who had developed lung cancer

3,062 who had not developed lung cancer

They were grouped by:

Smoking behavior

Age

Gender

Years since they stopped smoking

The study was performed in Caucasians to minimize the effect of ethnic genetic variations.

What’s next?

Further studies in African-American populations with different SNP patterns may help define which of the five genes close to chromosome 15 causes lung cancer.

Once a region has been further defined, subsequent DNA sequencing of blood samples from individuals with lung cancer will begin, to find the single mutation that influences lung cancer risk.